7 Major Diseases Cured by Using Garlic

This article throws light upon the seven major cured solved by using garlic. The diseases are: 1. Atherosclerosis and Lipid Metabo­lism 2. Fibrinolytic Activity 3. Platelet Aggregation 4. Blood Pressure Lowering Effect 5. Diabetes Mellitus 6. Antioxidant Effects 7. Arrhythmia and Others Cardiovascular Ef­fects.

Disease # 1. Atherosclerosis and Lipid Metabo­lism:

Atherosclerosis is a complex disease, character­ized by an excessive inflammatory, fibro-fatty, proliferative response to damage of the artery wall involving several cell types, particularly smooth muscle cells, monocyte-derived macrophages, T- lymphocyte and platelets.

Hyperlipidemia constitutes a major etiopathological factor for atherosclerosis. The medicinal val­ue of garlic is best known for its lipid lowering and anti-atherogenic effects.

Animal Studies:

Several groups of investigators studied the effects of long term (2-9 months) feeding of garlic and garlic preparations (2% garlic powder in diet) on experimental atherosclerosis induced by a high- cholesterol diet in rabbits.

Most of these studies reported a statistical­ly significant reduction in atheromatous lesions, particularly in the aorta, that averaged about 50%. The chronic effects of garlic on lipid metabolism in rats were also encouraging.

The duration of these studies was at least 4 weeks. Garlic (1-4% in diet) and garlic protein administration in hypercholesterolemia rats induced by a high-cholesterol diet, significantly reduced serum choles­terol, triglyceride and LDL cholesterol but there was no effect on se­rum HDL.

Total lipid content and cholesterol lev­els in liver were also decreased in rat after chron­ic garlic consumption. Abramoviz et al. (1999) investigated the effect of allicin as an active com­ponent of garlic on the formation of fatty streaks in aorta and lipid profile in mice.

While no significant differences were observed between blood lipid profiles, the micro­scopic evaluation of formation of fatty streaks in the aortic sinus showed that values for mice in the allicin treated groups were significantly lower by nearly 50%.

Aged garlic extract ‘Kyolic’ also sig­nificantly inhibited the development of thickened, lipid-filled lesions in the preformed neointimas produced by balloon-catheter injury of the right carotid artery in cholesterol-fed rabbits.

Human Studies:

Since 1975 there have been more than 46  human studies on lipid-lowering effects of garlic and garlic preparations. These stud­ies, were mostly randomized, double blind, pla­cebo-controlled using garlic powder rather than raw garlic of 4-16 weeks, in hyperlipidemia pa­tients.

Most of these studies showed significant decrease in serum cholesterol and serum triglyc­eride. Only about one-third of these studies meas­ured lipoproteins, where significant favorable changes in LDL-cholesterol level (11-26% de­crease) were consistently observed.

A few studies using garlic powder (having low allicin yields) failed to show any lipid lowering effects. During the last one decade (1993-2002), 18 clinical stud­ies have been published regarding the hypolipedemic effect of garlic. Nine studies showed nega­tive results and garlic powder was used in seven of these studies.

The different composition and quantity of sulfur com­ponents of different garlic preparations used in various studies could account for the inconsistent findings. It highlights the need for standardization of different garlic preparations and to arrive at a valid conclusion.

Other factors might include the subject recruitment, duration of study, dietary con­trol, lifestyle and methods of lipid analyses.

Four meta-analysis of randomized, placebo-controlled human studies on hypocholesterolemic effects of garlic are available. The analyses further detected that the extent of cholesterol-lowering properties of garlic differed markedly from one study to an­other.

Warshafsky and his colleagues deduced from five randomized clinical trials that hypercholesterolemia patients treated with garlic had a mean plasma cholesterol concentration, that was 9% lower than that of patients treated with place­bo. Silagy and Neil (1994) analysed sixteen trials, with data from 952 sub­jects in the meta-analysis.

Garlic, in powder and non-powder form, signifi­cantly lowered serum lipid levels over a 1-3 month period. Serum cholesterol fell by 8% with dried powder preparations and 15% with non-powder preparations. Serum triglyceride level also dropped significantly, while HDL-cholesterol was essen­tially unchanged.

Amongst the garlic powder prep­arations these effects appeared to be similar across the daily dose range of 600-900 mg. Another meta-analysis revealed that there was no significant difference in the mean concen­trations of serum lipids, lipoproteins or apo Al or B amongst the groups receiving garlic (900 mg/ day of dried garlic powder standardized to 1.3% allicin) and placebo.

In this meta-analysis, garlic was less effective in reducing total cholesterol than suggested by previous meta-analyses.

However, in a more recent meta-analysis of thirteen trials, garlic reduced total cho­lesterol level from baseline significantly more than placebo, while six diet controlled trials with the highest scores for methodological quality revealed a non-significant difference between garlic and placebo groups.

The available data suggests that garlic is superior to placebo in reducing total cho­lesterol levels. However, the size of the effect is modest, and the robustness of the effect is debata­ble.

Therefore, the hypocholesterolemic effect of garlic remains to be firmly established. In contrast, cardiovascular calcification (CAC), a marker of atherosclerosis, is inhibited by garlic. A recent small pilot study showed that, compared with pla­cebo, AGE may inhibit the rate of progression of CAC in the general population.

Possible Mechanisms:

Protective effect of garlic on atherosclerosis has been attributed to its capacity to reduce lipid con­tent in arterial wall. Garlic causes direct anti-ather­ogenic (preventive) and anti-atherosclerotic (caus­ing regression) effects at the level of artery wall.

Garlic depressed the hepatic activities of lipogenic and cholesterogenic enzymes such as malic enzyme, fatty acid synthase, glucose-6 phosphate dehydrogenase and 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase. Garlic also in­creased the excretion of cholesterol, as manifest­ed by enhanced excretion of acidic and neutral steroids after garlic feeding.

LDL isolated from human subjects giv­en AGE and aqueous garlic extract was found to be significantly more resistant to oxidation. These data indicate that sup­pressed LDL oxidation may be one of the power­ful mechanisms accounted for the benefits of gar­lic in atherosclerosis.

Allicin was identified as the active compound responsible for anti-atheroscle­rotic effect. Allicin affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by mac­rophages.

Other in vitro stud­ies revealed that water-soluble organosulfur com­pounds, especially S-allyl cysteine (SAC), present in aged garlic extract and diallyl-di-sulfide (DADS), present in garlic oil are also potent inhibitors of cholesterol synthesis. Inhibition of blood vessel calcification might be another promising mecha­nism of anti-atherosclerotic effect of garlic.

Disease # 2. Fibrinolytic Activity:

Inhibition of fibrinolytic activity (FA) or deficien­cy of the factors involved might upset the hemo­static balance and allow excessive fibrin deposi­tion. In diabetes, hypertension and hypercholes­terolemia, it is possible that disturbance in the coagulation-fibrinolytic system may bean impor­tant factor leading to the development of throm­bosis and ischemia.

Accordingly, the greater the FA, the more favorable is the antithrombic effect. FA is generally determined by euglobulin lysis time. The patients who died with acute or old myocardial infarction showed the highest values of plasma fibrinogen, euglobulin lysis time and anti-plasmin.

This suggests that prognosis in myo­cardial infarction is partly influenced by the de­gree to which plasma fibrinolysis is impaired.

Animals Studies:

Marked rise in blood coagulability of rabbits that followed 3 months of cholesterol feeding (0.2 g/ kg/day) was significantly reduced by the essential oils of garlic. Fibrinolytic activity was actually in­creased even above the normal control levels. The essential oils of garlic (equivalent to 1 g/kg/day of raw bulbs) proved effective in mediating fibrino­lytic activity.

Experimental study also revealed that garlic juice (raw garlic; 250 mg/day) had significant effect in enhancing the fibrinolytic activity in rabbit after receiving a cholesterol rich diet for 13 weeks. The plasma fibrinolytic activity in rabbit, which was decreased on cholesterol feeding, was considerably increased when this diet was sup­plemented with garlic.

Human Studies:

Almost all human studies on fibrinolytic activity of garlic have been found to have positive effect. Acute as well as chronic intake of garlic oil and raw garlic increased fibrinolytic activity (FA). In 1975, Bordia first demonstrated that garlic oil in­creased FA after 3 hours of administration.

Bordia also reported that chronic (3 weeks to 3 months) administration of garlic oil (dose: equivalent to 1 gm/kg of fresh garlic) increased FA significantly ranging from 36% to 130% in healthy as well as acute myocardial infarction patients.

Dried garlic powder has been also tested for its fribinolytic activity. While two stud­ies showed no difference in FA, one study showed increased FA as well as tissue plas­minogen activator activity after acute and chron­ic garlic powder intake.

Chutani and Bordia (1981) designed one study to show that both raw arid fried garlic significantly enhance FA. Frying removes the strong acrid smell of garlic, but preserves it useful effects on FA.

The rise in FA has been observed within 6 hours of garlic administration, which showed that garlic has a rapid onset of action and the effect is well main­tained as long as garlic is being taken. Recently Bordia (1998) found that intake (3 months) of ethyl acetate extract of crushed raw garlic also increased FA.

Disease # 3. Platelet Aggregation:

Platelet aggregation superimposed on an athero­sclerosis vessel is an antecedent event causing total blockage of blood flow leading to myocardial in­farction and thromboembolic diseases. Platelets adhere to the exposed collagen, laminin and von Willebrand factor in the injured vessel wall. This process is called platelet activation.

Activation can also be produced by ADP and thrombin. The acti­vated platelets change shape, put out pseudopodia, discharge their granules, and stick to other platelets, initiating the process of platelet aggre­gation.

Aggregation is also fostered by platelet activating factor (PAF), a cytokine secreted by neutrophil and monocytes as well as platelets. Studies have shown that garlic has great potential in inhibiting platelet aggrega­tion.

Animal Studies:

Pretreatment of rabbits with an aqueous extract of garlic (500 mg/kg) significantly inhibited throm- boxane-B2 (TXB2) synthesis (a potent platelet ag­gregator) and protected against thrombocytopenia induced by collagen or arachidonate infusion.

These observations indicate that garlic may be beneficial in the prevention of thrombosis. Aqueous extract of garlic was found to inhibit platelet aggregation induced by ADP, epinephrine, collagen and arachidonate in a dose- dependent manner in vitro and inhibited biosyn­thesis of prostacyclin in rat aorta.

A dose-dependent inhibition of cyclooxygenase activity and collagen-induced platelet aggregation was observed in rabbit platelets treated with raw garlic in vitro. The concentration required for 50% inhibition of the platelet aggregation for garlic was calculated to be approximately 6.6 mg/ml plas­ma. But boiled garlic was found to be of little ef­fect.

This finding indicates that garlic may be ben­eficial in the prevention of thrombosis if ingested raw rather in a cooked form. Garlic extract containing diallyl disulfide and diallyl tri- sulfide, prevented acute platelet thrombus forma­tion in stenosed canine coronary arteries.

Fresh garlic extract is effective in reducing thromboxane formation by platelets both in vivo and in vitro animal models of throm­bosis.

It was observed that garlic inhibits thrombin-induced platelet synthesis of TXB2 in a dose-and time-dependent manner in rabbits. Maximum in­hibition of TXB2 occurred between 0.5 h and 6 h at 25 and 100 mg/kg garlic.

The rapid recovery of platelet cyclooxygenase activity after infusion of a single dose of garlic suggests that garlic should be taken more frequently in order to achieve ben­eficial effects in the prevention of thrombosis.

Garlic was also capable of delaying hyperthermia-induced platelet aggre­gation in mouse pial arterioles, in vivo, which was comparable to acetyl salicylic acid. Ajoene, a constituent of essential oil of garlic, has been shown to inhibit in vitro platelet aggregation in different species of animals i.e. cow, dog, guinea-pig, horse, monkey, pig, rabbit and rat.

Under in vivo flow conditions and in the presence of phys­iological calcium levels, ajoene prevented throm­bus formation induced by severe vascular dam­age, mainly in arterial sites with local low shear stress.

Makheja and Bailey (1990) identified three main antiplatelet constituents, namely adenosine, allicin and polysulfides in garlic. Adenosine and allicin both inhibited platelet aggregation without affecting cyclooxygenase and lipoxygenase metabolites of arachidonic acid.

The polysulfide’s inhibited plate­let aggregation as well as thromboxane synthesis. The observed in vivo antiplatelet effects of ingest­ing garlic are attributable more to adenosine than to allicin and polysulfide constituents.

Human Studies:

In human studies a positive response to garlic has been observed. Like enhancement of fibrinolysis, garlic also has a beneficial effect on platelet ad­hesion or aggregation in human. Bordia (1978) first showed the dose dependent inhibition of platelet aggregation by garlic.

Raw garlic, garlic oil and other extract of garlic have been shown to inhibit platelet aggregation in in vitro induced by ADP, collagen, arachidonate, epinephrine and calcium ionophore. Single dose as well as chronic intake of garlic powder and garlic oil also inhibits platelet aggregation.

Possible Mechanisms:

The antiplatelet mechanism of garlic is much more established than its any other biological effects. Aqueous extract of garlic inhibited platelet aggre­gation induced by ADP, collagen, arachidonate, epinephrine and calcium ionophore A23187 in a dose-dependent manner.

It was found that garlic reduced the formation of throm­boxane, inhibited the phospholipase activity and lipoxygenase products formed in platelets. These effects may explain, in part, inhibition of platelet aggregation.

Further, since garlic was also effec­tive in inhibiting aggregation induced by calcium ionophore A23187 it may be suggested that the anti-aggregation effect may be related to intra-platelet mobilization of calcium. Inhibition of epinephrine-induced aggregation by garlic extract may suggest that it may be inhibiting uptake of calci­um into platelets thereby lowering cytosolic cal­cium concentrations.

In regard to a specific mechanism of ajoene’s antiplatelet action, several suggestions have been made. Ajoene strongly inhibits the metabolism of arachidonic acid by both cyclooxygenase and lipoxygenase pathways, thus inhibiting the synthesis of thrombox­ane A2 and 12-HETE.

Anti-aggregatory effect of ajoene may also be causally related to its direct interaction with the putative fibrinogen receptor (GPIIb/lla).

The studies of Jamaluddin et al. (1988) demonstrated that ajoene interacts with a purified hemoprotein im­plicated in platelet activation. Ajoene modifies the binding of the hemoprotein with ligands deemed to be physiologically relevant as effectors. Allicin inhibits human platelet aggregation in vitro with­out affecting cyclooxygenase or thromboxane syn­thase activity or cyclic adenosi ne monophosphate (AMP) levels.

Allicin also inhibits platelet aggre­gation but does not alter the activity of vascular prostacyclin synthase. However, it inhibits iono­phore A23187-stimulated human neutrophil lys­osomal enzyme release. Thus garlic appears to be in possession of components which might exert their effects at various stages involved in the proc­ess of platelet aggregation.

Disease # 4. Blood Pressure Lowering Effect:

A general definition of hypertension is a systolic blood pressure (SBP) of 140 mm Hg or higher or a diastolic blood pressure (DBP) of 90 mm Hg or higher or both. Prevention and proper manage­ment of hypertension decreases the incidence of related morbidity and mortality. A downward shift of 3 mm Hg in SBP decreases the mortality from stroke by 8% and from ischemic heart disease by 5%.

Life style modification are definitive therapy for some and adjunctive therapy for all persons with hyperten­sion. Diets that are high in fruits, vegetables and low-fat dairy products; have been shown to reduce hyperten­sion.

Increased consumption of garlic is associat­ed with lower incidence of hypertension in popu­lation. Based on current information, garlic pow­der preparations are considered for recommen­dation as adjuncts in the treatment of hyperten­sive patients.

Animal Studies:

In experimental animals, intravenous injection of garlic extracts produced slight reductions in both systolic and diastolic pressures. Oral administration of garlic reduced ex­perimentally induced hypertension, bringing blood pressure back to the normal range. For example 2.5 to 25 mg per kg of alcoholic garlic extract reduced blood pressure by 10 to 50 mm Hg.

Blood pressure in dogs has been significantly reduced for several hours fol­lowing intragastric administration of a small dose of garlic powder (as low as 2.5 mg/kg b.wt).

Other animal experiments on rats and dogs also indicate a ‘normalizing’ effect of garlic on elevated blood pressure. The antihypertensive effect of gar­lic in these studies has been repeatedly confirmed.

Allicin, a major constituent of garlic, was also evaluated for its antihypertensive effects. Chronic oral administration of allicin lowered blood pres­sure in hypertensive rats. Allicin also caused pulmonary vasodilatation in isolated lung of rat.

Single as well as multiple doses of aqueous garlic extract reduced thromboxane B2 and prostaglandin E2 level and thereby reduced hypertension in ‘2 kidney 1 -clip’ model of hypertension in rat. Garlic also inhibited endothelin-1 induced contraction in a dose-dependent manner in iso­lated rat pulmonary arteries.

Garlic (100 mg/kg) administration for 5 days resulted in a complete inhibition of acute hypoxic pulmonary vasoconstriction in rat (Fallon et al., 1998). There was a marked decrease in systolic blood pressure in spontaneously hypertensive rats after oral administration of single dose of garlic.

Prolongation of life span was also found in hypertensive rats by dietary sup­plementation with garlic.

Human Studies:

Leoper and DeBray recognized the hypotensive effect of garlic in 1921. Damrau (1941) has reviewed the earlier literature, including his own investigations on 26 patients.

Blood pressure reduction was observed in 85% of the patients, the average decline being 12.3 mm Hg systolic (SBP) and 6.5 mm Hg diastolic (DBP) blood pressure, over one-quarter of the subjects experienced a decline in SBP of 20 mm Hg or more.

Piotrowski (1948) has reviewed some of the early clinical studies in which garlic was admin­istered under controlled conditions to hyperten­sive patients. Two-fifths of 100 patients exhibited a 20 mm Hg or greater decline in SBP generally within 1 week after initiation of treatment with 0.6 to 1.2 g daily of dialyzed, alcoholic garlic ex­tract.

Studies with a dried garlic powder (Kwai tab­lets) showed an average decrease in blood pres­sure of about 9% with 0.6 g garlic powder per day and in a rand­omized double blind trial, a beneficial effect of garlic on blood pressure and blood lipids in mild­ly hypertensive subjects was demonstrated.

Those reports point in the same di­rection, that garlic can be useful in the control of mild hypertension in many if not all cases. Pektov (1979) has also cited several studies, mostly from the Soviet Union and Bulgaria, which indicate that garlic and its extracts exhibit antihypertensive ac­tivity.

Besides subjective improvement, the results of these studies indicated a moderate hypotensive effect involving a drop in SBP of 20-30 mm Hg and in DBP of 10-20 mm Hg.

Another study in China (1986) on 70 hypertensive patients who were given garlic oil equivalent to 50 gm of raw garlic/day, 47 patients showed moderate to marked reduction in blood pressure (Zheziang Institute of Traditional Chinese Medicine, 1986).

There is only one meta-analysis done by Silagy and Neil (1994). Eight trials were identified all using the same dried garlic powder preparation (Kwai). Data from 415 subjects were included in the analysis.

Only three trials were specifically conducted in hypertensive subjects. Of the seven trials that compared the effect of garlic with that of placebo, three showed a significant reduction in systolic blood pressure (SBP) and four in diasto­lic blood pressure (DBP).

The overall pooled mean difference in the absolute change (from baseline to final measurement) of SBP was greater in the subjects who were treated with garlic than in those treated with placebo.

For DBP the corresponding reduction in the garlic-treated subjects was slight­ly smaller. This meta-analysis suggest that this “gar­lic powder preparation may be of some clinical use in subjects with mild hypertension”.

Howev­er, there is still insufficient evidence to recommend it as a routine clinical therapy for the treatment of hypertensive subjects. More rigorously designed and analyzed trials are needed for firm conclu­sion.

Possible Mechanism/s:

Rashid and Khan (1985) have postulated that mechanism of antihypertensive action of garlic is due to its prostaglandin like effects, which decreas­es peripheral vascular resistance. The gammaglutamylcysteines are the compounds in garlic that may lower blood pressure, as indicated by their ability to inhibit angiotensin-converting enzyme in in vitro.

Garlic modulates the production and function of both endothelium derived relaxing and constricting factors and this may contribute to its protective effect against hy­poxic pulmonary vasoconstriction.

Garlic elicits nitric-oxide-dependent relaxation in pulmonary arteries. This hypothesis was explained by the fact that NG-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor) abolished the vasodilatory effect of garlic.

But another study report­ed that pulmonary vasodilatory effect of allicin are independent of the synthesis of NO, ATP-sensitive (K+) channel, activation of cyclooxygenase enzyme.

Disease # 5. Diabetes Mellitus:

Diabetes mellitus is a group of diseases charac­terized by high blood glucose levels resulting from defects in insulin secretion, insulin action, or both. Abnormalities in the metabolism of carbohydrate, protein, and fat are also present. Nutrition plays a primary role to control blood glucose level and further complication.

Animal Studies:

Garlic was effective in reducing blood glucose in streptozotocin-induced as well as alloxan-induced diabetes mellitus in rats and mice. Most of the stud­ies showed that garlic can reduce blood glucose level in diabetic mice, rats, and rabbit.

Augusti & Sheela consistently showed that S-allyl cysteine sulfoxide (alliin), a sulfur containing amino acid in garlic (200 mg/kg b.wt.) has a potential to reduce diabetic condition in rat almost to the same extent as did glibenclamide and insulin.

Treat­ment of diabetic rats with garlic oil decreased se­rum acid and alkaline phosphatase, serum alanine and asparate transferases, as well as serum amy­lase in diabetic rats. Aged garlic extract is also effective to prevent adrenal hyper­trophy, hyperglycemia and elevation of corticosterone in hyperglycemic mice induced by immo­bilization stress.

Garlic in­take (6.25% by weight in diet) for 12 days reduced hyperphagia and polydipsia but did not alter hy­perglycemia and hypoinsulinaemia in streptozo­tocin-induced diabetic mice. Ingestion of garlic juice resulted in better utilization of glucose in glucose tolerance test per­formed in rabbits.

The ethyl alcohol, petroleum ether and ethyl ether extracts of garlic produced a significant fall in blood sugar levels in rabbits. Allicin at a dose of 250 mg/kg is 60% as effective as tolbutamide in alloxan-induced diabetic rabbit.

Human Studies:

Hypoglycemic effect of garlic in human is not well studied. Chronic feeding of garlic oil and garlic powder showed significant decrease in blood glu­cose level whereas some other studies showed no change of blood glu­cose level.

All human studies, except one or two, showing effect of garlic on blood glucose level on normal healthy individuals but not in diabetic patients. Thus the role of garlic in diabetic condi­tion is yet to be confirmed.

Possible Mechanism/s:

Though the exact mechanism/s of garlic as antid­iabetic agent is still not clear but invivo as well as invitro studies showed that garlic acts as an insulin secretagogue in diabetic rats.

Augusti & Sheela also proposed that antioxidant effect of S-allyl cysteine sulfoxide (isolated product from garlic) may also contribute for its beneficial effect in diabetes.

Another proposed mechanism is due to spare insulin from sulphydryl group. Inac- tivation of insulin by sulphydryl group is a com­mon phenomenon. Garlic (allicin) can effectively combine with compounds like cysteine and en­hance serum insulin.

Jain & Vyas proposed that garlic can act as an anti-diabetic agent by increasing either the pan­creatic secretion of insulin from the beta cells or its release from bound insulin.

Disease # 6. Antioxidant Effects:

Oxidative stress plays a pathological role in the development of heart failure. Oxidative stress caused specific morphological changes of mito­chondria, excess formation of superoxide (O₂), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility.

Administration of antioxi­dants or agents which mimic cardiac endogenous antioxidants may reduce the progression of heart failure. The beneficial ef­fect of garlic in heart might be partly through its antioxidant activity.

Animal Studies:

Garlic extracts and its component have direct free radical scavenging activity as shown by different invitro studies. LDL isolat­ed from allicin-treated (one component of raw garlic extract) groups was more resistant to CuSO₄ induced oxidation than LDL isolated from control mice. Incubation of mouse plasma with (3) H-labeled allicin showed binding of allicin to lipoproteins.

Raw garlic homogenate augmented endogenous antioxidants along with reduction of basal lipid peroxidation in rat heart, liver and kidney in a dose dependent manner.

Aged garlic extract (AGE) also exerted its antioxidant action by scavenging reactive oxygen species and enhancing the cellular antioxi­dants, like reduced glutathione, superoxide dismutase, catalase and glutathione peroxidase of vascular endothelial cells.

Augmented endogenous antioxidants on heart and endothelial cells have important direct cytoprotective effects, especially in the event of oxidant stress induced injury.

Recently, in our laboratory, we found that chronic oral administration of garlic homogenate protected rat heart from in vitro ischemic reperfusion injury and oxida­tive stress induced by single dose of Adriamycin and isoproterenol.

AGE has been shown to offer protection against the cardiotoxic effects of doxo­rubicin, an antineoplastic agent used in cancer therapy. Feeding of garlic powder in rats for 11 days had a protective effect on isoproterenol-induced myocardial damage.

Aqueous garlic extract was also found to be effective in reducing Cu (+)- initiated oxidation of low density lipoprotein (LDL) as measured by photo-chemiluminescence meth­od (Lewin and Popov, 1994). AGE also protected vascular endothelial cells from H₂O₂-induced oxidant injury.

Human Studies:

One human study show that ingestion of garlic leads to significantly lowered plasma and eryth­rocyte MDA (a byproduct of lipid peroxidation) levels and to increased activities of some antioxi­dant enzymes, which indicates that consumption of garlic decreases oxidation reactions.

Another human study suggests that garlic preparation may be tentatively used as an adjunct agent in treatment of arterial hypertension because of its hypolipemic and antioxidant properties.

It is quite possible that in­creased endogenous antioxidants and reduced peroxidation processes due to garlic consumption may play a part in some of the beneficial effects of garlic in elderly subjects and might be true for all other organ as suggested in experimental stud­ies.

One case study from Nepal reported that garlic (9 months treatment) prevented heart failure of a 50 year old breast can­cer patient from adriamycin treatment. As the mechanism of adverse effects is due to oxidative stress, improvement of heart failure suggests the antioxidant effect of garlic.

In con­trast to above reports, one human study with 2 weeks treatment of Aged Garlic extract in coro­nary artery disease did not change the markers of oxidant stress (plasma oxidized low density lipo­protein and peroxides) and systemic inflammation (plasma C-reactive protein ad interleukin-6).

Possible Mechanism/s:

Direct free radical scavenging activity of garlic extracts and its component was responsible for antioxidant activity of garlic. Augmentation of endogenous antioxidant enzymes might be anoth­er possible mechanism for cardio protective effect of garlic against oxidative stress.

Disease # 7. Arrhythmia and Others Cardiovascular Ef­fects:

Animal Studies:

Garlic has a significant antiarrhythmic effect in both ventricular and supraventricular arrhythmi­as. Garlic powder (1% added to a standard chow for an 8 week period) significantly reduced ischemia reperfusion-induced ventricular fibrilla­tion (VF) in isolated perfused rat heart.

Size of the ischemic zone was significant­ly reduced and the onset of arrhythmia after oc­clusion of the descending branch of the left coro­nary artery was significantly prolonged in rats fed with a standard chow enriched with 1% garlic powder for 10 weeks.

Garlic dialysate suppressed premature ventricular con­tractions and ventricular tachycardia in ouabain-intoxicated dogs as well as ectopic rhythms in­duced by isoprenaline and aconitine on electri­cally driven left rat atria. Garlic dialysate decreased the positive inotropic and chronotropic effects of isoproterenol in a concen­tration dependent manner, β-receptor blocking ac­tion of garlic was also suggested by Martin et al.

The positive inotropism and chronotorpism in­duced by isoproterenol were partially antagonized by preincubation of the rat atria with the garlic dialysate. The ECC showed a regular sinus brady­cardia rhythm in garlic dialysate fed anaesthetized rat.

Direct relaxant effect of cardiac muscles was reported by Aqel et al., (1991). Garlic juice inhibited norepinephrine-induced contractions of rabbit and guinea pig aor­tic rings.

It also inhibited the force of contraction of isolated rabbit heart in a concentration-depend­ent manner. In contrast, one study showed that aqueous garlic extract increased the amplitudes of atrial complex ‘p’ wave and the ventricular complex ‘QRS’ of the rat ECG. This is suggestive of increase in voltage output of the atria and ventricles probably in accordance with posi­tive inotropism.

Human Studies:

Aortic stiffening is as much an important risk fac­tor in cardiovascular morbidity and mortality, as it serves as reliable surrogate marker for clinical endpoints like myocardial and cerebrovascular incidents.

Elevated aortic stiffness induces high systolic blood pressure, augmented pulse pressure with increased ventricular afterload, reduced sub­endocardial blood flow and augmented pulsatile stress in the peripheral arteries.

In population, consuming garlic for long period, attenuation of age-related increase in aortic stiffness has been observed. This suggests a protective effect on the elastic proper­ties of the aorta related to aging in human. This study also showed that regular long term garlic powder intake protected endothelial cell from oxidative injury.

Twelve week therapy with garlic powder (800 mg/ day) was effective in patients with peripheral ar­terial occlusive disease Stage II. A significant de­crease of plasma viscosity was observed. It is also quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment.

Microcirculation of skin increased by 48% after administration of 800 mg/day garlic powder over a period of four weeks. Plasma viscosity was decreased by 3.2%. Kiesewetter also reported that garlic improved blood fluidity and increased capillary perfusion.

Decreased plasma vis­cosity and increased (55%) capillary skin perfusion were observed even after 5 hours of garlic pow­der administration.